Antimalarial activity of quassinoids

In Vivo Antimalarial Activity of Quassinoids in Murine Models. 3787... 

The investigation of the antimalarial properties of quassinoids then restarted at a significant rate in the mid-1980s and has remained relatively constant since then. Review articles on the antimalarial activity of quassinoids were published by Muhammad and Samoylenko in 2007 [59] and Guo et al. in 2005 [47]. 

Trager W, Polonsky J (1981) Antimalarial activity of quassinoids against chloroquine-resistant Plasmodium falciparum in vitro. Am J Trop Med Hyg 30 531... 

Trager, W., and J. Polonsky Antimalarial Activity of Quassinoids against Chloroquine-Resistant Plasmodium falciparum in vitro. Am. J. Trop. Med. Hyg. 30 (3), 531 (1981). 

Cachet N, Hoakwie F, Bertani S, Bourdy G, Deharo E, Stien D, Houel E, Gomitzka H, Fillaux J, Chevalley S, Valentin A, Jullian V (2009) Antimalarial activity of SimaUkalactone E, a new quassinoid from Quassia amara L. (Simaroubaceae). AntimiCTob Agents Chemother 53 4393 398... 

The discovery of antiparasitic activities of quassinoids (see Sect. 4) prompted some authors to study the antimalarial potential of these molecules [61]. Among the quassinoids highlighted as potential antimalarials by Trager and Polonsky were simalikalactone D, identified as the most active molecule with complete inhibition of parasite growth at a dose of 2 pg ml , as well as glaucarubinone and soularubinone. Other compounds, such as sergeoUde [62] and bmceantin [63], also showed significant antiplasmodial activity. 

Table 125.1 In vivo antimalarial activity of natural and semisynthetic quassinoids against ...

O Neill MJ, Bray DH, Boardman P, Phillipson JD, Warhust DC, Peters W, Suffness M (1986) Plants as sources of antimalarial drugs in vitro antimalarial activities of some quassinoids. Antimicrob Agents Ch 30 101... 

Figure 5 Biological activities associated with quassinoids, from Simaroubaceae species, may not be linked to a common mechanism of action/ Different testing procedures have indicated insecticidal activity for quassin, anticancer activity for quassimarin (also present in Quassia amara) and antimalarial activity for simalikalactone-D/...

Many activities in quassinoid area were due partly to the fact these natural products possess a wide spectrum of biological properties including in vivo antileukemic, antiviral, antimalarial, antifeedant, and amoebicidal activity. 

Among the antimalarial active quassinoids, bruceolide (248) is one of the representative compounds as a common core skeleton. 

Crude extracts of the root bark from Celastrus paniculatus Willd. (Celastraceae) demonstrated significant activity against cultured P. falciparum (93), and the active principle was shown to be pristimerin, a quinonoid triterpene. The family Simaroubaceae has also yielded a number of compounds with in vivo and in vitro antimalarial activity (94-96) including quassinoids. Bruceantin has been most extensively studied, but is very cytotoxic however, other quassinoids are relatively less toxic to cultured KB cells while retaining potent antimalarial activity (88). Plants from the Meliaceae are commonly used as febrifuges in Africa, and several limonoids from this family, such as nimbolide and gedunin, have also been found to produce moderate inhibition of cultured P. falciparum (97,98). 

In a previous paper [1], we reviewed the isolation of quassinoids, alkaloids, and fatty acids from Simaroubaceous plants during the period 1972-1988 and discussed their biological activities, such as antitumor, antimalarial, and anti-inflammatory agents as well as insect antifeedants, amoebicides, and herbicides. This review will add new quassinoids isolated from Simaroubaceous plants from 1988 onwards and their biological activities, for example, antitumor, anti-tumor-promotor (= inhibitor against TPA-induced EBV-EA activation), anti-HIV, anti-tuberculosis, and insect antifeedant activities. Furthermore, the stability of quassinoids, lower activities of degradation products, and the synthesis of fluorinated quassinoids are also described. 

Low BS, Teh CH, Yuen KH, Chan KL (2011) Physico-chemical effects of the major quassinoids in a standardized Eurycoma longifolia extract (Fr 2) on the bioavailability and pharmacokinetic properties, and their implications for oral antimalarial activity. Nat Prod Commun 6 337-341... 

Compared with the plethoric studies on antiplasmodial activity against P. falciparum in vitro, in vivo antimalarial assays dedicated to quassinoids are scarce and hardly comparable. Nevertheless, the excellent antimalarial activities highlighted in those studies should open the way to complementary studies of their pharmacokinetics and toxicity. Association with other antimalarials should also be investigated in order to define new therapeutic schemes and to lower the administered doses, increasing drugs tolerability. 

An earlier publication mentioned that the reported traditional antimalarial activity was not confirmed in quassinoids. More recent reports, however, showed that the methanol and hexane extracts of Q. amara exhibited strong antimalarial activity in mice infected with Plasmodium berghei The activity was comparable to that of chloroquine and was later attributed to the presence of the quassi-noid simalikalactone D. ... 

Quassinoids are bitter components produced by members of the Simaroubaceae. They exhibit diverse biological activities including anticancer, antimalarial, insecticidal, and phytotoxic activities. Ailanthone (26), chaparrinone (27), and other quassinoids, along with indole alkaloids, contribute to the invasiveness of the Chinese tree tree-of-heaven Alianthus altissima Swingle), in Europe.15... 

Quassinoids have attracted much attention due to the wide spectrum of biological activities that they display, viz., antimalarial, antifeedant, anti-inflanunatory, antiulcer, antipyretic, antifertility, antileukemic, cytotoxic activities, and induction of murine stem cell differentiation which have been widely reported [54-59]. We have demonstrated that quassin is a potent immunomodulatory tool that efficiently controls the estabhshment of leishmanial parasite within the host macrophages [60]. Our contention was that quassin could be used as a potential inununomodulator to generate the required immunity not only for the treatment of leishmaniasis but also for the treatment of other chronic infectious diseases. Subsequently, we had shown that both quassin and neoquassin can be used along with artesunate (a derivative of artemisinin) as combinatorial therapy against malaria [61]. 

Francois G, Diakanamwa C, Timperman G, Bringmann G, Steenackers T, Atassi G, Looveren MV, Holenz J, Tassin JP, Assi LA, Vanhaelen-Fastre R, Vanhaelen M (1998) Antimalarial and cytotoxic potential of four quassinoids from Hannoa chlorantha and Hannoa klaineana, and their structure-activity relationships. Int J Parasitol 28 635-640... 

The quassinoids are renowned for two major pharmacological activities their anticancer and their antiplasmodial potential. Looking more closely at the evolution of publications on these two major classes of biological activities, we obtained the curves shown in Fig. 125.8. The linear regressions represented here demonstrate an early interest in their anticancer activities (1970-1985) and the increasing interest in their antimalarial potential (since 1990). Subsequent sections will therefore focus on these two pathologies. 

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